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Chediak-Higashi syndrome
Last reviewed: 20.11.2021
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Chediak-Higashi syndrome (Chediak-Higashi syndrome, CHS) is a disease with generalized cellular dysfunction. The type of inheritance is autosomal recessive. Due to a defect in the Lyst protein. A characteristic feature of this syndrome is giant peroxidase-positive granules in neutrophils, eosinophils, peripheral blood monocytes and bone marrow, and in granulocyte precursor cells. Giant granules are also found in circulating lymphocytes, cytoplasm of neurons and cells of connective tissue of the perineural region.
Chediak-Higashi syndrome is a rare disease characterized by severe repeated purulent infections, partial albinism, progressive neuropathy, a tendency to bleeding, development of lymphoproliferative syndrome, and the presence of giant granules in many cells, especially in peripheral blood leukocytes. Immunodeficiency in Chediak-Higashi syndrome is caused, first of all, by a violation of the phagocytosis function in granulocyte and macrophage cells and is shown to be prone to purulent and fungal infections. Bleeding is associated with a defect in the release of granulocytic granules.
The first mention of the Chediak-Higashi syndrome dates back to 1943 (Beguez Cesar). Further descriptions we find in Steinbrinck 1948, Chediak 1952 and, finally, in Higashi 1954.
[Pathogenesis of Chediak-Higashi syndrome
The pathogenesis of the disease is associated with an anomaly in the structure of cell membranes, a violation of the system of collective microtubules, and a defect in the interaction of the latter with the membranes of lysosomes. Most of the clinical manifestations can be explained by the abnormal distribution of lysosomal enzymes. The frequency and severity of pyogenic infections is due to a decrease in the activity of oxygen metabolism and intracellular digestion of microbes in phagocytes due to delay and unstable release of hydrolytic lysosomal enzymes from giant granules to phagosomes. In addition, in patients, the activity of natural killers and antibody-dependent cytotoxicity of lymphocytes are reduced. The disease is attributed to primary immunodeficiency.
Symptoms of Chediak-Higashi syndrome
Clinical manifestations of Chediak-Higashi syndrome are recurrent piogenic infections, partial albinism of hair, skin and eyes, photophobia are characteristic. Soon after birth, the torpid phase of the disease occurs, associated with the anomaly of the formation of antibodies to the Epstein-Barr virus. Clinically against the background of a bacterial or viral infection, a secondary hemophagocytic syndrome develops; fever, pancytopenia with hemorrhagic syndrome, lymphadenopathy, hepatosplenomegaly, neurological symptoms - episodes of seizures, impaired sensitivity, paresis, cerebellar disorders, mental retardation. The forecast is unfavorable.
Diagnosis of Chediak-Higashi syndrome
The diagnosis of Chediak-Higashi syndrome is based on the detection in the smear of peripheral blood of characteristic giant granules in neutrophils, eosinophils and other granulosa-containing cells. When examining a bone marrow smear in leukocyte progenitor cells, giant inclusions are found that are peroxidazopositive and contain lysosomal enzymes, suggesting that these are giant lysosomes or, in the case of melanocytes, giant melanosomes.
Diagnosis of Chediak-Higashi syndrome
Treatment of Chediak-Higashi syndrome
In the treatment of Chediak-Higashi syndrome, symptomatic measures are taken, protecting the skin and eyes from insolation. In the treatment of infectious episodes - a combination of broad-spectrum antibiotics. With the development of hemophagocytosis, polychemotherapy with the inclusion of glucocorticoids (mainly dexamethasone), vincristine, etoposide, endolumbar injections of methotrexate, replacement therapy with blood components is indicated. The only radical method of treatment, as with many other primary immunodeficiencies, is the allogeneic bone marrow transplantation.